RESTORATION OF T CELL RESPONSIVENESS TO INTERLEUKIN-2 IN RECIPIENTS OF PANCREATIC ISLET XENOGRAFTS TREATED WITH CYCLOSPORINE

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Abstract
The immunosuppressive mechanism of cyclosporine (CsA) was studied using pancreatic islet xenotransplantation. A dose of 40 mg/kg/day CsA significantly prolonged survival of hamster islet grafts in BDE rats to 14.0 ± 7.1 days compared with 2.0 ± 0.9 days in controls (P < 0.01), and antihamster lymphocytotoxic antibody was not detected in recipient sera even after rejection. Responses of spleen cells to pokeweed mitogen (PWM) and to phytohemagglutinin (PHA) were inhibited at least 21 days after transplantation in recipients treated with CsA. The addition of exogenous interleukin-2 (IL-2) to spleen cell cultures on day 7 had no effect on the impaired response to PHA. At the time of graft rejection (day 14), the T cell response to PHA recovered with the addition of IL-2. However, significant changes were not observed in the ratio of spleen cell subpopulations, which were studied with monoclonal antibodies of W3/ 13, OX-12, W3/25, and OX-8. From these results we conclude that CsA can significantly prolong islet xenograft survival in closely related species, and inhibit the production of humoral antibodies and T cell responses. At the time of graft rejection, recipient T cell responsiveness to IL-2 was restored. This suggests that islet xenograft rejection is caused by the recovery of cellular immunity in recipients treated with CsA.